Ultrasound contrast agents: balancing safety versus efficacy

Abstract

In October, 2007, the FDA issued a new ‘black box’ warning, several new disease state contraindications and a mandated 30-min post-procedure monitoring period for the ultrasound contrast agents Definity^® (perflutren lipid microsphere injectable suspension, Lantheus Medical Imaging, North Billerica, MA, USA) and Optison^™ (perflutren protein type A microspheres for injectable suspension, GE Healthcare, Buckinghamshire, UK). These labeling changes were largely secondary to reports of 4 patient deaths, and ∼ 190 other ‘serious cardiopulmonary reactions’ that were temporally related but not clearly causally attributable to Definity administration. Contrast agent use in the US plummeted in the immediate aftermath of this FDA action, with many hospitals, physician offices and outpatient imaging centers suspending contrast echocardiography altogether. This review will focus on the immediate response from the international physician community, new contrast agent safety data published within the past year, results of a special meeting of the FDA Cardio-Renal panel devoted to contrast agent safety in June 2008, recently issued revised product labeling for both agents and future prospects for contrast echocardiography.

Keywords::

• black box warning
• contrast echocardiography
• contrast enhanced ultrasound
• Definity^®
• FDA
• Optison^™
• ultrasound contrast agents